Triterpenes are classified into amylin, lupeol, nosterol and squalene groups. These are all compounds which are insoluble in water and soluble in oil, organic solvents or the like.
The triterpenes are widely distributed in throughout the plant kingdom in the form of a free radical and bound with sugar into saponin or with acid into ester. The amylin group of the triterpenes, which is represented by a chemical formula having an OH-radical at the third position and a COOH-radical at the seventeenth position is a compound as represented by the following formula [1]. The compounds thereof are typically oleanolic acid, ursolic acid and hederagenin as concretely shown in Table 1 below.
The oleanolic acid mentioned above is variously found in a beet in the form of saponin and in the leaves of an olive, a green perilla, a jujube, and a ground ivy, the peel of an apple, the germ of a clove and so on. The ursolic acid is obtained from not only fruit such as an apple and a cherry and waxy coat material of the leaf thereof, but also the leaves of the ground ivy, jujube tree and so on. Furthermore, hederagenin is found in hedera helix, the fruit of a soapberry and so on. ##STR1## wherein, R.sub.1 represents CH.sub.3 or CH.sub.2 OH, R.sub.2 represents H or OH, R.sub.3 represents H or CH.sub.3, R.sub.4 represents H or CH.sub.3, and R.sub.5 represents H or OH.
TABLE 1 ______________________________________ Compound R.sub.1 R.sub.2 R.sub.3 R.sub.4 R.sub.5 ______________________________________ Amylins Oleanolic acid CH.sub.3 H CH.sub.3 H H Ursolic acid CH.sub.3 H H CH.sub.3 H Pomolic acid CH.sub.3 H H CH.sub.3 OH Hederagenin CH.sub.2 OH H CH.sub.3 H H Echinocystic acid CH.sub.3 OH CH.sub.3 H H ______________________________________
On the other hand, there have been recently carried forward investigations as to substances having pharmacological functions in various plants including medicinal herbs by research laboratories of universities, public and private research institutions and nongovernmental laboratories. Then, it has been confirmed that the amylins of a triterpene group present in a plant, which is represented by a chemical formula having an OH-radical at the third position and a COOH-radical at the seventeenth position, shows pharmacological activity such as antibiosis relative to a tumor, hepatitis, inflammation and caries. Various types of amylin groups have been so far reported in academic societies and in literatures, reviewed in news papers and magazines and proposed by patents.
The inventors of the present invention have also conducted experiments on the pharmacological function of oleanolic acid obtained from a sugar beet and confirmed that the oleanolic acid has the effects of antibiosis to a tumor and hepatitis, cariostatic (insoluble glucanynthesis inhibition) and so on.
Further, as a use of oleanolic acid, there have been proposed compositions for use in the mouth on the basis of the pharmacological function of oleanolic acid (Japanese Patent Publication No. SHO 63-26083).
However, as these triterpenes are insoluble in water, the pharmacological experiments as mentioned above were conducted using specimens obtained by dissolving the triterpene into an organic solvent such as dimethyl sulfoxide (hereinafter referred as to DMSO), ethanol, propylene glycol, and butanediol so as to make the "in vitro" and "in vivo" tests no matter how coarse or fine the triterpene applied therefor is.
There are a good many cases of using particularly DMSO having the high boiling point and high solvent power as the organic solvent applied for the tests as noted above. However, the DMSO is not approved as an additive to foods, drinks or compositions for use in the mouth. Also, the other organic solvents are not satisfactory when being used as a food additive.
Also, the compositions for use in the mouth proposed in the aforenoted Japanese Patent Publication No. SHO 63-26083 do not contain oleanolic acid in the water-soluble state. Therefore, a product obtained from the compositions conventionally proposed shows scarcely the effect of cariostatic and is unmarketably.
One of the inventors of the present invention has proposed a process for producing oleanolic acid from beet pulp (Japanese Patent Application Public Disclosures Nos. SHO 60-268189 and SHO 60-268190), and tried to provide oleanolic acid of high purity with solubility in water weight losing its pharmacological function in order to add oleanolic acid to foods, drinks, compositions for use in the mouth or the like. However, there has not yet been produced the intended compound having high deprived of the pharmacological function of oleanolic acid.
The inventors of the present invention have further proposed a method for producing compositions for use in the mouth by completely dissolving oleanolic acid in ethanol, glycerin, propylene glycol, menthol or the like and combining the solution resultantly obtained with other compositions, on the basis of the fact that oleanolic acid is a little soluble in an organic solvent such as ethanol which is known as a pharmacological solvent (Japanese Patent Appln. Public Disclosure No. HEI 1-290619). However, the proposed method has suffered a disadvantage that compositions thus obtained are unstable in effect, and oleanolic acid contained therein becomes insoluble in water with time.
Also, the pharmacological experiments were carried out by causing oleanolic acid to be dissolved into water or emulsified by use of surface active agents of various types such as fatty ester (nonionics) and ampholytic surface active agent (derived from natural substance). However, the "in vitro" test the inventors conducted reveals that almost all of the surface active agents have no effect of cariostatic. Even in the case of the surface active agents showing a little effect of cariostatic, its effect was remarkably scattered, and moreover, the reproductivity thereof could not been accomplished.
As the result of making the progress in the inventors' elaborate studies, there has been found that a new composition which is soluble in water while keeping the effect of cariostatic shown by the triterpenes in its active condition can be produced by subjecting triterpene having oleanolic acid to inclusion with cyclodextrin (hereinafter referred to as CD).
Though solubilization or emulsification of the triterpenes by use of the surface active agent as touched upon above has been generally accomplished, there has not yet been published a report on a method of subjecting triterpene to inclusion with CD for the purpose of making water-soluble of triterpenes while maintaining the inherent functions of triterpene in its active state.